Incorporation of ROS-Responsive Substance P-Loaded Zeolite Imidazolate Framework-8 Nanoparticles into a Ca2+-Cross-Linked Alginate/Pectin Hydrogel for Wound Dressing Applications

Purpose: Wound healing, especially of extensive full-thickness wounds, is one of the most difficult problems in clinical studies. In this study, we prepared a novel substance P (SP)-delivery system using zeolite imidazolate framework-8 (ZIF-8) nanoparticles. Methods: We synthesized ZIF-8 nanoparticl...

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Bibliographic Details
Published in:International journal of nanomedicine 2020-01, Vol.15, p.333-346
Main Authors: Zhu, Yiming, Yao, Zuochao, Liu, Yushu, Zhang, Wen, Lele Geng, Ni, Tao
Format: Article
Language:English
Subjects:
Aqueous solutions
Cell culture
Cellulose acetate
Gas absorption
Glycerol
hydrogel
Hydrogels
metal-organic framework
Nanoparticles
Original Research
Penicillin
Polyethylene glycol
Scanning electron microscopy
Sodium
substance p
Transmission electron microscopy
Wound healing
Zeolites
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Summary:Purpose: Wound healing, especially of extensive full-thickness wounds, is one of the most difficult problems in clinical studies. In this study, we prepared a novel substance P (SP)-delivery system using zeolite imidazolate framework-8 (ZIF-8) nanoparticles. Methods: We synthesized ZIF-8 nanoparticles using a modified biomimetic mineralization method. We then coated SP-loaded ZIF-8 nanoparticles (SP@ZIF-8) with polyethylene glycol-thioketal (PEG-TK) to fabricate SP@ZIF-8-PEG-TK nanoparticles, and encapsulated them in injectable hydrogel composed of sodium alginate and pectin and cross-linked using calcium chloride. The final hydrogel wound dressing containing SP@ZIF-8-PEG-TK nanoparticles was called SP@ZIF-8-PEG-TK@CA. Results: The fabricated ZIF-8 nanoparticles had high SP-loading efficiency. SP-release assay showed that the SP@ZIF-8-PEG-TK nanoparticles maintained drug activity and showed responsive release under stimulation by reactive oxygen species. The SP@ZIF-8-PEG-TK nanoparticles promoted proliferation of human dermal fibroblasts, up-regulated expression levels of inflammation-related genes in macrophages, and exhibited favorable cytocompatibility in vitro. Full-thickness excision wound models in vivo confirmed that SP@ZIF-8-PEG-TK@CA dressings had excellent wound-healing efficacy by promoting an early inflammatory response and subsequent M2 macrophage polarization in the wound-healing process. Conclusion: In conclusion, these findings indicated that SP@ZIF-8-PEG-TK@CA dressings might be useful for wound dressing applications in the clinic.
ISSN:1176-9114
1178-2013
1178-2013
DOI:10.2147/IJN.S225197